On August 22, 2011, the FDA approved the combination of Pegasys and Copegus for the treatment of chronic hepatitis C virus (HCV) infection in pediatric patients 5 through 17 years of age with chronic hepatitis C (CHC) virus infection who have compensated liver disease and have not been previously treated with interferon alpha.. Pegasys/Copegus combination treatment for HCV in adults was approved in December, 2002, and that original approval included a postmarketing requirement to evaluate the drugs in pediatric patients.
Hoffmann-La Roche Inc submitted the results of Study NV17424 to support the use of Pegasys/Copegus in pediatric patients. Subjects participating in the study received Pegasys at a dose of BSA x 180 mcg/1.73 m2 once weekly plus Copegus at a dose of approximately 15 mg/kg/day in two divided doses. Study participants received 24 weeks of blinded treatment and were determined to be responding or not responding based on undetectable HCV RNA (< 50 IU/mL). Responders continued their assigned treatment to 48 weeks regardless of HCV genotype. Nonresponders were unblinded and either stopped treatment (if they were in the Pegasys/Copegus group) or rolled into a “compassionate” Pegasys/Copegus combination group to continue 48 weeks of treatment (if they were in the Pegasys/placebo group). Subjects were followed off-treatment for an additional 24 weeks after the completion of 48 weeks of treatment to assess the primary efficacy endpoint, the proportion of subjects achieving sustained virologic response (SVR), defined as undetectable HCV RNA at 24 weeks post-treatment. Any subject switching from randomized Pegasys/placebo to the compassionate combination Pegasys/Copegus was counted as a treatment failure. The trial enrolled 114 previously untreated pediatric subjects 5 through 17 years of age (of whom 55% were less than 12 years old who were randomized to receive either combination treatment of Pegasys/Copegus or Pegasys/placebo. The initial randomized arms were balanced for demographic factors: 55 subjects received initial combination treatment of Pegasys/Copegus and 59 received Pegasys/placebo. In the overall study population, 45% were female, 80% were Caucasian, and 81% were infected with HCV genotype 1. As previously shown in adults, the combination of Pegasys/Copegus provided significantly better response rates as measured by SVR compared to treatment with Pegasys alone. The SVR rate for study subjects receiving Pegasys/Copegus was 53% (29/55) compared to 20% (12/59) in the group receiving Pegasys. Subjects with the more difficult to treat genotype 1 receiving Pegasys/Copegus demonstrated SVR of 47% (21/45) while the smaller subgroup with non-genotype 1 had higher SVR (80%, 8/10). The safety profile of Pegasys with or without Copegus in pediatric subjects in the clinical trial was similar to that observed in adults receiving similar treatment. Seven subjects receiving combination Pegasys/Copegus treatment for 48 weeks discontinued therapy for safety reasons (depression, psychiatric evaluation abnormal, transient blindness, retinal exudates, hyperglycemia, type 1 diabetes mellitus, and anemia). Dose modifications because of adverse events and laboratory abnormalities occurred commonly in the pediatric trial, about 35% during the randomized treatment period in both arms. The most common reason for modification of Pegasys was neutropenia and the most common reason for dose reduction of Copegus was anemia. The most common non-serious treatment related adverse events reported among subjects receiving Pegasys/Copegus included influenza-like illness (91 %), headache (62%), gastrointestinal disorders (56%), injection site reactions (45%), irritability (31%), fatigue (27%), rash (20%), pruritis (15%), and insomnia and decreased appetite (13% each). The most important pediatric-specific safety issue related to Pegasys/Copegus was growth delay. Pediatric subjects treated with Pegasys/Copegus combination therapy experienced a delay in gaining weight and height after 48 weeks of therapy compared with baseline. Both weight and height for age z-scores as well as the percentiles of the normative population for subject weight and height decreased during treatment. At the end of 2 years follow-up after treatment, most subjects had returned to baseline normative growth curve percentiles for weight and height. At 2 years post-treatment, 16% of subjects remained 15 percentiles or more below their baseline weight curve and 11% remained 15 percentiles or more below their baseline height curve. Richard Klein Linda Lewis
Office of Special Health Issues
Food and Drug Administration
Division of Antiviral Products
Food and Drug Administration
| This email was sent to list-fda@xxxxxxxxxxx using GovDelivery, on behalf of: U.S. Food & Drug Administration (FDA) · 10903 New Hampshire Ave · Silver Spring, MD 20993 · 800-439-1420 |  |
